Ferenc Jaroslav, Papasaikas Panagiotis, Ferralli Jacqueline, Nakamura Yukio, Smallwood Sebastien, Tsiairis Charisios D
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
University of Basel, Petersplatz 1, 4001 Basel, Switzerland.
Sci Adv. 2021 Dec 10;7(50):eabj6897. doi: 10.1126/sciadv.abj6897.
Mechanical input shapes cell fate decisions during development and regeneration in many systems, yet the mechanisms of this cross-talk are often unclear. In regenerating tissue spheroids, periodic osmotically driven inflation and deflation cycles generate mechanical stimuli in the form of tissue stretching. Here, we demonstrate that tissue stretching during inflation is important for the appearance of the head organizer—a group of cells that secrete the Wnt3 ligand. Exploiting time series RNA expression profiles, we identify the up-regulation of Wnt signaling as a key readout of the mechanical input. In this system, the levels of Wnt3 expression correspond to the levels of stretching, and Wnt3 overexpression alone enables successful regeneration in the absence of mechanical stimulation. Our findings enable the incorporation of mechanical signals in the framework of patterning and highlight the broad significance of mechanochemical feedback loops for patterning epithelial lumens.
在许多系统的发育和再生过程中，机械输入塑造细胞命运决定，但这种相互作用的机制往往不清楚。在正在再生的组织球体中，周期性渗透驱动的膨胀和收缩循环以组织拉伸的形式产生机械刺激。在这里，我们证明膨胀过程中的组织拉伸对于头部组织者（一群分泌Wnt3配体的细胞）的出现很重要。利用时间序列RNA表达谱，我们确定Wnt信号的上调是机械输入的关键读数。在这个系统中，Wnt3的表达水平与拉伸程度相对应，并且仅Wnt3的过表达就能在没有机械刺激的情况下实现成功再生。我们的发现能够将机械信号纳入模式形成框架，并突出了机械化学反馈回路对上皮管腔模式形成的广泛意义。
